Despite the best clinical vigilance, secondary exposure to harmful microorganisms can occur in hospital settings, where the routine prescription of antibiotics leads to the development of drug-resistant bacteria. Such exposure to harmful microorganisms commonly result in wound infections and sepsis (infection combined with systemic inflammation), complicating the treatment of many types of diseases and injuries, as well as the management of invasive medical techniques, including surgery, catheterization, and use of mechanical ventilation.
In the United States more than 750,000 cases of sepsis occur each year, resulting in the loss of more than 200,000 lives, making it the 10th leading cause of death in the United States. Furthermore, the average cost of sepsis care is approximately $25,000 per episode, and as high as $92,000 per pediatric patient for fungal bloodstream infections. For cancer patients alone, the total cost of treating sepsis has been reported to be $3 billion/year. Overall annual health care costs of sepsis in the United States are estimated to be $16.7 billion. Detection of infection at the earliest possible stage, and intervention with appropriate antibiotic treatment, will greatly reduce mortality and health care costs.
Wound infections have been found to cause production of nitric oxide (NO) in the wound. Accordingly, the detection of wound infections could be accomplished via detection of NO production in and/or adjacent to the wound. However, it has been found that high NO activity sets in soon after the onset of an infection, but that the high (elevated) NO activity persists in the wound only for about 25-30 minutes, after which the levels of NO are drastically reduced again. Therefore, to reliably detect infection in wounds, detection of NO in the wound must be carried out at the onset of infection.
Although not related to wound infection detection, since it is known that NO plays essential roles in mammalian life, there have been attempts to develop sensors for measuring NO in biological systems. The success of these attempts have been hampered by the fact that NO rapidly oxidizes to nitride and/or nitrate in the presence of oxygen, and that the half life of NO in healthy biological tissues is very short (i.e., ˜30 seconds). Different conventional methods for measuring NO in biological systems, and the deficiencies thereof, are shown in Table I below:
TABLE IConventional Methods for Measuring NO, and Their DrawbacksTechniqueIn-situNon-invasiveCapture and freezeAmperometricNoYesNoFluorescenceNoYesNoGreiss Reaction AssayNoYesNoElectrochemicalYesNoNoCurrent ProposalYesYesYes
It has been shown that it is possible to detect a host response (a natural defensive reaction of the body to infection) to early experimentally induced sepsis minutes after the introduction of bacterial components or whole bacteria in a rat (as shown in FIG. 1) and a baboon (as shown in FIG. 2). These measurements were taken using an invasive electrochemical method, wherein the electrode was directly dipped into the wound. However, there are currently no non-invasive methods of measuring the transient amount of NO produced in a wound upon the onset of bacterial infection. Accordingly, it is an object of the present invention to develop a device and method for non-invasively detecting the production of NO in a wound, so as to detect the onset of infection and/or sepsis thereon.
It is a further object of the invention to provide a bandage comprising a non-invasive, calorimetric detector, which can be directly placed above the wound (for example, as part of a bandage), and which will exhibit a persistent change in color when NO activity in the wounds becomes high, so as to alert a user or caregivers of the onset of infection in the wound.